Dynamic expression of H19 and MALAT1 and their correlation with tumor progression biomarkers in a multistage hepatocarcinogenesis model

Hepatocellular carcinoma (HCC) progresses sequentially in a stepwise pattern. Long noncoding RNA (lncRNA) can regulate the complex cascade of hepatocarcinogenesis. Our study aimed to elucidate the expression profile of H19 and MALAT1 during the different stages of hepatocarcinogenesis and the correlation between H19 and MALAT1 with the genes implicated in the carcinogenesis cascade. We employed a chemically induced hepatocarcinogenesis murine model to mimic the successive stages of human HCC development. Using real-time PCR, we analyzed the expression patterns of H19 and MALAT1, as well as the expression of biomarkers implicated in the Epithelial-Mesenchymal transition (EMT). The protein expression of the mesenchymal marker vimentin was also evaluated using immunohistochemistry in the stepwise induced stages. The histopathological evaluation of the liver tissue sections revealed significant changes during the experiment, with HCC developing at the final stage. Throughout the stages, there was a dynamic significant increase in the expression of H19 and MALAT1 compared to the normal control. Nevertheless, there was no significant difference between each stage and the preceding one. The tumor progression biomarkers (Matrix Metalloproteinases, vimentin, and beta-catenin) exhibited the same trend of steadily increasing levels. However, in the case of Zinc finger E-box-binding homeobox 1 and 2 (ZEB1 and ZEB2), the significant elevation was only detected at the last stage of induction. The correlation between lncRNAs and the tumor progression biomarkers revealed a strong positive correlation between the expression pattern of H19 and MALAT1 with Matrix Metalloproteinases 2 and 9 and vimentin. Our findings imply that genetic and epigenetic alterations influence HCC development in a stepwise progressive pattern.

Automated summary

This study aimed to investigate the expression profile of H19 and MALAT1 during different stages of hepatocarcinogenesis and their correlation with genes involved in carcinogenesis cascade. A murine model of chemically induced hepatocarcinogenesis was used. Real-time PCR was employed to analyze the expression patterns of H19, MALAT1, and epithelial-mesenchymal transition (EMT) biomarkers. The results showed a significant increase in the expression of H19 and MALAT1 throughout the stages compared to the normal control. Tumor progression biomarkers exhibited a similar increasing trend, while Zinc finger E-box-binding homeobox 1 and 2 (ZEB1 and ZEB2) showed a significant elevation only at the last stage of induction. The correlation analysis revealed a strong positive correlation between the expression pattern of H19 and MALAT1 with Matrix Metalloproteinases 2 and 9 and vimentin. This study suggests that genetic and epigenetic alterations contribute to hepatocellular carcinoma development in a stepwise progressive pattern.